Justin Zaghi

of Abeta oligomers. The current investigation tested if ICV introduction of anti-ADDL antibody would overcome the transient nature of the anti-Abeta antibody and would produce long-lasting preventive effects in the TgCRND8 transgenic mouse model of AD. Methods: Cerebral amyloid load was quantitated by immunocytochemistry and ELISA. Synaptic degeneration was evaluated by immunocytochemistry. Results: Results show that anti-ADDL antibody persistently reduced cerebral amyloid by 3-fold as evaluated by immunocytochemistry and ELISA; further, a significant reduction in synaptic degeneration ( 55%), as evaluated by immunocytochemistry of a 25-kDa presynaptic molecular marker SNAP-25 critical to calcium mediated synaptic vesicular exocytosis involved in EPSP and long term potentiation (LTP), was maintained up to 8 weeks post injection. Conclusions: The data indicate that passive immunization with antiADDL antibody may be an improved strategy to prevent early synaptic deficits in AD and to delay AD-like pathology and suggest the value in developing simpler means for introducing these antibodies into the brain.